The Leuven Experience with a Dichotomy in Bronchiolitis Obliterans Syndrome (bos) after Lung Transplantation Revealed by Azithromycin

WINNING ABSTRACT: BOS is the most important cause of late mortality after LTx. Until 5 years ago, the prevalence was around 30% and 50%, 3 and 5 years after LTx. Introduction of azithromycin (AZI) improved the FEV1 in 40% of BOS patients. AZI treatment may explain why in our center, the BOS prevalence at 3 years has decreased from 30% to 15% compared to the ISHLT registry. Opposed to the current belief about BOS, we hypothesize a dichotomy within BOS: Neutrophilic Reversible Allograft Dysfunction (NRAD) and fibropoliferative BOS (fBOS; table 1). This dichotomy is based on the discrepancy in AZI response and observations within our center consisting of clinical, biochemical and cellular (BAL) analysis. NRAD makes a re-evaluation of the BOS definition (irreversible FEV1 decline, neutrophilic inflammation, fibroproliferation) indispensable. As it is reversible, NRAD should be excluded from BOS and accepted as innate (non-specific) inflammation and as an important risk factor for the development of BOS. So after exclusion of other complications such as acute rejection, infection, gastro-oesophageal reflux and after a trial with AZI, BOS will remain what it is now (the fBOS). This implements a reevaluation of the neutrophilic inflammation, as it is a prerequisite for AZI responsiveness. BOS can then histologically be characterized as pure inactive OB, which is hardly responsive to any treatment.